Table 2. Selected recent anti-HIV-1 therapeutic vaccine studies in HIV-1-positive and healthy individuals.
| Vaccine type | Vaccine | Immune responses | Viral load | Reference | ||||
|---|---|---|---|---|---|---|---|---|
| Viral vector | ||||||||
| ALVAC | Recombinant canary pox viral vector genetically engineered to express HIV-1 Gag and Pro (subtype B LAI strain) and CRF01_AE (subtype E) HIV-1 gp120, administered to uninfected individuals | Weak evidence of increased CD4+ T-cell count upon HIV-1 infection | No overall statistically significant reduction in pre-HAART viral load upon HIV-1 infection | [2,55] | ||||
| MVA-B | A recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B | Polyfunctional CD8+ and CD4+ T-cell responses along with Env-specific antibody responses in 95% of volunteers | Uninfected volunteers | [58] | ||||
| NYVAC | Phase I trial of NYVAC, expressing Gag, Pol, Nef, and Env from an HIV clade B isolate injected intra- muscularly into 10 HIV-infected patients successfully treated with antiretroviral therapy | Increased HIV-specific T-cell responses in virtually all vaccines, mostly GAG-specific pre-existing and new detected responses | Not studied | [59] | ||||
| Ad35-GRIN | Andovirus vector containing GAG, reverse transcriptase, intergrase, Nef, and Env | Polyfunctional HIV-specific cellular immune responses and humoral responses | Uninfected volunteers | [61] | ||||
| AVX101 | Alphavirus replicon containing GAG | Limited immune responses | Uninfected volunteers | [62] | ||||
| DNA | ||||||||
| PENNVAX DNA | Three plasmids expressing ENV, GAG and Pol, plasmid containing IL-12 | Developed CD4+ or CD8+ T-cell responses after repeat vaccination | Uninfected volunteers | [63] | ||||
| DermaVir | Dose escalation study of plasmid DNA containing 13 complete and 2 non-functional HIV-1 genes/ proteins that self-assemble | Induction of significantly increased GAG-specific T-cell responses | Not studied | [66] | ||||
| GTU-multi-HIVB | Phase II trial of fusion gene expressing Rev, Nef, TAT, GAG + CTL epitopes clusters from Pol and Env. Intradermal and Intramuscular vaccination of in HIV-1-infected ART-naïve patients | The increase in HIV-1-specific CD4 T-cells was observed predominantly in the TNF-α-secreting CD4 T-cell population while both HIV-1-specific TNF-α and IFN-γ CD8 T-cell populations increased following immunization. | IM group with a decrease in log pHIV-RNA 0.47 log units (95% CI from −0.75 to −0.19) compared with placebo (P = 0.001) | [68,69] | ||||
| Dendritic cell | ||||||||
| DCV2/MANON07-ORVACS | Autologous DC pulsed with whole inactivated HIV-1 | Increased HIV-1-specific T-cell responses | Decrease of plasma viral load setpoint ≥1 log was observed in vaccinated groups and was associated with a consistent increase in HIV-1-specific T-cell responses | [71] | ||||
| mRNA- electroporated DC | mRNA vaccine encoding Tat, Rev, and Nef | Induced and/or enhanced HIV-1- specific CD4+ and CD8+ T-cell but did not correlate with the number of weeks off cART | Viral load in plasma unchanged from historical control data | [72,73] | ||||
| Sub unit | ||||||||
| Vacc4X | Four modified peptides from the GAG protein containing MHC class I and II restricted epitopes | Delayed-type hypersensitivity (DTH) reactions. T-cell responses in 80% to 90% of patients allowing for structured treatment interruption | Significantly improved viral load ratios for DTHhi (compared with DTHlo) groups: 0.58 (0.27-1.33) and 1.26 (0.90-2.02). Correlate with stable CD4+ T-cell counts | [74-78] | ||||
| Subdominant HIV-1 peptides and CAF01 | Multiple subdominant epitopes restricted to HLA supertypes | Induction of CD4+ and CD8+ T-cell responses | No significant changes in viral load | [79] | ||||
| TAT | Whole TAT protein | Modified pattern of CD4+ and CD8+ T-cell activation and decreased markers of immune activation | Subjects on ART during study | [80] |
ALVAC, canarypoxvirus; ART, antiretroviral therapy; cART, combination antiretroviral therapy; CI, confidence interval; DC, dendritic cell; HAART, Highly Active Antiretroviral Therapy; IFN-γ, interferon-gamma; IL, interleukin; IM, intramuscular; MHC, major histocompatibility complex; MVA-B, modified vaccinia virus Ankara vector expressing Env, Gag, Pol, and Nef proteins of HIV-1 subtype B; NYVAC, New York Vaccinia virus; TNF-α, tumor necrosis factor-alpha.